Aliphatic Nitriles, which are extensively used in industry, present an important environmental hazard. Although aliphatic nitriles are potent CNS toxins, their toxic actions on other organ systems differ. Yet little is known about the in vivo biologic fate of these chemicals other than a proportion of the administered dose is converted to cyanide which is excreted as thiocyanate. Our objective is to elucidate the total biologic fate of the aliphatic nitriles, acetonitrile, propionitrile and BetaBeta-dimethylaminopropionitrile, particularly to determine the distribution at target tissue sites and the extent of interaction at these sites. Also to determine in vivo the extent of cyaninde liberation as well as other metabolic reactions. Radiolabeled compounds will be used to monitor the uptake, tissue distribution and excretion of these compounds as well as its molecular interactions. Sites and possible enzymatic mechanisms of their metabolism will be characterized. Effect of treatments known to alter acute aliphatic nitriles toxicity on it biologic fate will be examined. These studies will provide a clearer understanding of the relationships between the toxicity of these aliphatic nitriles and biotransformation, begin to define the molecular events responsible, and guide future studies of the chemical mechanisms underlying the toxicity of structurally related aliphatic nitriles.